Introduction To Pharmacology Flashcards

(436 cards)

1
Q

What do we regulate in blood plasma?

A

Oxygen
Glucose
Ions
Volume

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2
Q

What do we regulate in interstitial fluid?

A

Glucose
Ions

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3
Q

What do we regulate in intracellular fluid?

A

ATP
Glucose
Ions
Volume

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4
Q

What is total body water?

A

42 L
~ 60%

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5
Q

How much water in blood plasma?

A

3L

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6
Q

How much water in interstitial fluid?

A

13L
- liquid surrounding cells

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7
Q

How much water in transcellular fluid?

A

1L
- CSF, lymph ect

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8
Q

How much water in intracellular fluid?

A

25L

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9
Q

What is the osmolality?

A

290 mOsm

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10
Q

What’s the distribution of ions ECF vs ICF?

A

ECF = more Na+, Cl-, Ca2+
ICF = more K+

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11
Q

What is amphipathic?

A

Have a region of polar and non-polar.
- Phospholipid bilayer

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12
Q

What is the cell membrane’s permeability?

A

Impermeable to large & charged.
Permeable to hydrophobic (O2, CO2, steroid hormones)

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13
Q

What are the two types of active transport?

A

Primary - direct - pumps using a chemical reaction
Secondary - indirect - cotransporters and exchangers - coupled uphill movement of one thing with downhill of another e.g. sodium potassium ATPase.

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14
Q

What is the effect of electrochemical gradients on transport?

A

Drives passive transport.
Depends on concentration gradient.
For charged molecules - also depends on voltage.

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15
Q

What is simple diffusion?

A

It is the movement of an uncharged hydrophobic solute through lipid bilayer.
How fast it moves = describes by flux (Jx)

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16
Q

What does flux (Jx) depend on?

A
  • permeability coefficient of X (Px)
  • concentration gradient
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17
Q

What is the flux equation?

A

Jx = Px(conc gradient)

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18
Q

What is a transmembrane protein?

A
  • an integral membrane protein
  • composed of membrane-spanning alpha helix domains
  • can be single pass or multipass
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19
Q

What defines a protein membranes topology?

A

Location of sequence

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20
Q

What are the types of transmembrane proteins?

A

Pore - non-gated channel
Channel - gated pore
Carrier
Pump - requires energy

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21
Q

What is a transmembrane protein?

A

All have multiple transmembrane segments surrounding a solute permeation pathway.
Allow hydrophilic molecules to pass the membrane.

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22
Q

What is the structure of a transmembrane protein?

A
  • Amphipathic helices - alternating hydrophobic and hydrophilic amino acids - hydrophobic surfaces face the membrane, hydrophilic surfaces create a central pore.
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23
Q

What do pores do?

A

Always open - facilitated diffusion
Have multiple subunits
e.g. aquaporins
Driving force = electrochemical gradient.

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24
Q

What does each channel have?

A

1) a moveable gate
2) a sensor: voltage, ligand, mechanical
3) a selectivity filter
4) an open channel pore

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25
What do carriers do?
Never has a continuous path. Driving force = electrochemical gradient Slow Can become saturated e.g. GLUT
26
How does carrier diffusion work?
1) The carrier is open to the outside 2) X enters and binds to binding site 3) Outer gate closes - X still bound 4) Inner gate opens 5) X enters cell
27
Why can carrier diffusion become saturated?
Flux limited by # of carriers and speed of carrier cycle. Jmax = conc high enough to occupy all carriers.
28
What carriers use active transport?
Pumps Cotransporters Exchangers
29
How do cotransporters work?
- Requires a solute whose electrochemical gradient provides the energy. - Move both in (symporters e.g. Na/glucose) - Can become saturated.
30
What is osmolality?
Total conc of all particles free in a solution. mOsm = milliosmoles per kg of water
31
What does a channel do?
Gated ion channels e.g. potassium channel. Driving force = electrochemical gradient
32
How do exchangers work?
Solutes move in opposite directions (antiporters e.g. Na/Ca).
33
What did Henry Dale do?
He won a Nobel prize for studying acetylcholine as an agent in the chemical transmission of nerve impulses.
34
What is a mediator?
A chemical, peptide or protein which communicates between cells.
35
What are the criterias for a mediator?
- released in sufficient amounts to produce a biological action on a specific cell in a time frame. - applying a sample will have the same biological effect - interference on synthesis, release or action will stop/control response.
36
What is the general path for mediators?
They are extracellular signal molecules --> bind to receptors on target cells --> initiates intracellular signals which alter cell behaviour through effector proteins (cell signalling)
37
What is signal transduction?
Converting extracellular signals to intracellular.
38
What are the five types of intercellular communication?
- contact-dependant - autocrine - synaptic - paracrine - endocrine
39
What is contact dependant signalling?
Shortest type of signalling. e.g. immune responses and development (delta-notch signalling)
40
What is paracrine signalling?
Extracellular mediators act locally - stored in vesicles or synthesised on demand. e.g. histamine, nitric oxide (vessel diameter), prostaglandins.
41
What is autocrine signalling?
Similar to paracrine but activates itself.
42
What is neuronal signalling?
Uses synapses - fast - to specific cells. Mediators - neurotransmitters e.g. ACh (neuromuscular junction &heart), Noradrenaline (on heart)
43
What is endocrine signalling?
Long distance - uses hormones through the blood. Slow and non-specific. Hormones can be protein (insulin), aa derives (adrenaline) or steroid (estradiol).
44
What two ways are mediators synthesised?
1) small molecular - regulated by specific enzymes. 2) peptides - regulated by transcription - depends what genes are active and cells can produce multiple types of mediator. Vesicles can store more than one.
45
What are the two groups of mediators?
- preformed and stored in vesicles until released by exocytosis - rapid - includes noradrenaline and insulin --> conc usually mM which is good so we can have high conc for response. - on demand synthesised and released by diffusion or constitutive secretion - slower to act - e.g. nitric oxide and prostaglandins.
46
How did we know that neurotransmitters are released in vesicles?
Studies showed quantal nature which suggested packages.
47
How does neurotransmitter action stop?
Enzymes can stop it e.g. acetylcholinesterase. The NT can also be taken back into the neuron or supporting cells e.g. glia - this is due to specific transporters in membrane
48
Who discovered acetylcholine?
Otto Loewi
49
How are noradrenaline and adrenaline made?
From tyrosine --> dopamine --> noradrenaline ---> adrenaline Enzymes required for each step.
50
What regulates both types of mediator release?
Calcium
51
What is a ligand?
Any molecule which binds to a receptor - can be antagonist or agonist Hydrophilic or hydrophobic
52
What is an endogenous agonist?
Mediator in the body which binds to a receptor - produces a response e.g. ACh, noradrenaline, insulin
53
What is converging cell signalling?
All cells have multiple types of receptors - can integrate information Receptors can use similar transduction mechanisms = amplify signal
54
What is diverging cell signalling?
Molecules can act on more than one type of cell type. Allows coordinated responses.
55
What are receptors?
Proteins - recognition sites which can bind to a molecule and modulate activity of the cell
56
What do the first three receptor classes have in common?
- each has transmembrane spanning segments - each has a ligand binding domain - ligands here are hydrophilic
57
What are the four classes of receptors?
1) Ligand-gated ion channels (ionotrophic) - could cause electrical signals - takes milliseconds 2) G protein-coupled receptors (metabotropic) - could contact muscles - takes seconds 3) Kinase-linked receptors - can change enzyme activity - takes hours e.g. insulin receptor 4) Nuclear (intracellular) - more channels in cell membrane - takes hours
58
What are nuclear receptors?
Polypeptides with multiple domains Ligands here are hydrophobic Act as a transcription factor - binds to DNA and regulated gene expression e.g. oestrogen receptors
59
Which chemical mediators use which receptors?
Most small mediators = ligand or g protein-coupled Peptide hormones = g protein-coupled or kinase-linked Steroid = nuclear
60
What are ligand-gated ion channels?
- Ion channels - involved in fast synaptic transmission - agonists = neurotransmitters - made of 3-5 subunits - had central aqueous pore - channel closes when agonist removed e.g. NAChR
61
What is nAChR?
Nicotinic Acetylcholine Receptor - excitatory ligand gated ion channel - on every skeletal muscle - in NMJ and autonomic NS - has 5 subunits - agonist = ACh or nicotine - when bind cause depolarisation as ions flow through
62
What is GABA?
Bind to ligand gated ion channels (GABAa receptors) - causes inhibition as cause hyperpolarisation
63
What is a G protein-coupled receptor?
- Single transmembrane protein which spans membrane 7 times (7TM) - >800 genes code for these - Interacts with an intracellular G protein (heterotrimeric GTP-binding protein) - has 1 alpha, 1 beta, 1 gamma subunit e,g, MAChR
64
What do the heterotrimeric g proteins do?
1) beta and alpha units are bound to the receptor 2) when ligand binds - g protein changes and causes GTP to bind to alpha instead of GDP 3) G protein leaves receptor 4) a-GTP and beta-gamma dissociate 5) they can bind with their effectors 6) when GTP --> GDP again - trimer reassembles
65
What are examples of effectors that G proteins may control?
- ion channels - enzymes: adenylyl cyclase, phospholipase C
66
What are secondary messengers?
Small diffusible molecules that spread a signal Amplify a signal
67
How is adenylyl cyclase modulated?
GAs - stimulates - more adenylyl cyclase, more cAMP and more protein kinase A GAi - inhibits - less adenylyl cyclase, less cAMP, less protein kinase A cAMP - secondary messenger
68
How do g proteins increase calcium levels?
Gaq (alpha subunit) activates phospholipase C which breaks down PIP2 into IP3 & DAG. IP3 triggers release of calcium from the ER.
69
What do specific G proteins do?
Gs - activates adenylyl cyclase - e.g. adrenergic B1/2 Gi - (a) inhibits adenylyl cyclase or (By) activates potassium channels - e.g. adrenergic a2/muscarinic M2 Gq - activates phospholipase C - increases calcium e.g. adrenergic a1/muscarinic M1/M3
70
What is a drug?
A known chemical substance which, when administered, causes a biological response. Can interfere with synthesis, storage, release, degradation or receptor-dependent response produced by a mediator.
71
What is an assay?
Lab test where we investigate the function of mediators, measure toxicity and test phamacological activity.
72
What are the principles of pharmacology?
- drug action must be explicable - drug molecules must be bound to cells/tissues to produce an effect - drug molecules must exert a chemical influence on 1 or more parts of a cell to produce a pharmacological response
73
What proteins are usually targeted by drugs?
- enzymes - transporters - ion channels - receptors
74
What is an antagonist?
Drug which inhibits the response of an agonist - competes with agonist and binds instead DO NOT MAKE A RESPONSE
75
When are side effects caused?
When drugs lack specificity - drugs will bind to its specific receptor anywhere.
76
What is therapeutic manipulation of contact-dependant signalling?
e.g. CAR T immunotherapy uses this signalling to kill cancer cells - engineered by altering genome of T cells
77
How is paracrine signalling affected by drugs?
e.g. mast cells secrete histamine - antihistamines will block histamine receptors e.g. prostaglandins (a type of eicosanoid) are formed from different enzymes - paracetamol can target these enzymes e.g. nitric acid relaxes blood vessels - viagra inhibits an enzyme - prolongs NO action
78
How can drugs target neurotransmission?
e.g. can block voltage gated sodium channels - prevent action potential - used as local anaesthetic - lidocaine e.g. Botulinum toxin - from bacteria - cleaves proteins needed for synapses e.g. amphetamines increase noradrenaline by displacing it from vesicles e.g. fluoxetine blocks 5HT reuptake - antidepressant
79
What are endocrine cells?
Hormones are secreted from here into blood. Have close proximity to capillary beds. Found in endocrine tissues or glands (NO DUCTS)
80
What is endocrine signalling?
Enables signalling along long distances Slow Specific to receptors - not specific organs or tissues
81
What are the different hormone types?
Protein e.g. Insulin Amino acid e.g. adrenaline Steroid e.g. estradiol
82
What is a peptide hormone?
- from amino acids - released by exocytosis by secretory granules - receptors = cell membrane surface - response - s to min
83
What are amino acid derived hormones?
- derived from tyrosine (requires specific enzymes) - released from vesicles via exocytosis (except thyroid hormone) - receptors = cell membrane surface (except thyroid hormone) - response = s to min (except thyroid)
84
What is a steroid hormone?
- metabolite of cholesterol (needs enzymes) - lipid soluble = diffuses out - diffuses into cells and binds to nuclear receptors - response = hours to days
85
What are the 7 endocrine glands?
- Pituitary - Thyroid - Parathyroid - Adrenals - Ovaries - Testes - Pancreas
86
What are endocrine tissues?
- hypothalamus - kidneys - GI tract - heart - liver - adipose tissue
87
What is the anterior part of the hypothalamus?
Adenohypophysis - developed from upward projection of pharynx - troph cells are stimulated by hormones from hypophyseal portal system from hypothalamic neurons
88
What is the posterior lobe of pituitary called?
Neurohypophysis - developed from downward projection of brain - releases hormones from large diameter neurones into bloodstream
89
What are the main pituitary hormones?
Tropic hormones - stimulate effects from other hormones - GH, ACTH, TSH, FSH, LH, Prolactin Posterior - ADH & Oxytocin
90
How is the thyroid an endocrine gland?
Secretes T3 & T4 (amino acid derived) - these depend on hypothalamic-pituitary hormones and iodine These transport across cell membranes by facilitated diffusion and bind to nuclear receptors. This regulated metabolism, development and growth
91
How is the parathyroid gland endocrine?
Parathyroid hormone (peptide) regulates plasma calcium and phosphate and targets bone, intestine and kidneys.
92
What is the feedback loop for PTH?
High plasma calcium is sensed by chief cells - lower PTH, lower kidney reabsorption, less bone resorption and low intestinal absorption.
93
What does adrenal cortex release?
Releases steroid hormones: glucocorticoid (cortisol), mineralcorticoid (aldosterone) Zona glomerulosa - mineral Zona fasciculata - gluco
94
What does the adrenal medulla release?
Chromaffin cells release adrenaline Noradrenaline is also released
95
What is the hypothalamic-pituitary-adrenocortical axis?
Hypothalamus releases CRH - this causes the anterior pituitary to release ACTH - causing adrenal cortex to release cortisol. Cortisol inhibits CRH and ACTH release
96
What do the ovaries secrete?
Steroid hormones: oestrogen and progesterone This gland can switch from negative to positive feedback
97
What do the testes secrete?
Leydig cells secrete steroid hormone - testosterone
98
What is the somatic NS route?
Somatic NS Afferent to CNS (brain and spinal cord) Efferent to somatic NS (voluntary) Skeletal muscles
99
What is the visceral nerve route?
Visceral nerves (sensory part of peripheral NS) Afferent to CNS Efferent to autonomic NS (involuntray - motor part of peripheral NS) Smooth muscle, cardiac, glands ect.
100
What are the parts of the autonomic nervous system?
(part of peripheral) Sympathetic - fight or flight - coordinated full body or organ specific Parasympathetic - rest and digest - organ specific
101
What are examples of sympathetic stimulation?
- eye - dilation - heart - increase heart rate - blood vessels - constricting - lungs - bronchiole dilatione - liver - reproductive systems
102
What are examples of parasympathetic stimulation?
- heart - decrease heart rate - eyes - GI tract - bladder - reproductive organs
103
How do parasympathetic and sympathetic work together?
Innervate the same tissues but have opposite effects - work synergistically. Except for sweat glands, hair, blood vessel sm and adrenal medulla which are mainly sympathetic
104
What is the structure of the autonomic nervous system?
Preganglionic neuron in CNS Postganglionic neuron in peripheral ganglion both symp and parasymp have this organisation
105
What are preganglionic neurons?
Always cholinergic - release ACh ACh activated nicotinic ACh receptors on postsynaptic cell
106
What is the sympathetic pathway?
Short cholinergic from thoracic and lumbar spinal cord - long adrenergic postganglionic Target tissue express alpha and beta adrenergic receptors
107
What is the exception to the sympathetic pathway?
Adrenal medulla - chromaffin cells are similar to postganglionic neurones but release adrenaline - target is a and b adrenergic receptors
108
What is the parasympathetic pathway?
Long cholinergic neurons from brainstem and sacral spinal cord Short cholinergic postganglionic neurones Target tissues express muscarinic ACh receptors
109
What is the vagus nerve?
Cranial nerve 10 Carries 80% of parasympathetic outflow Also carries visceral afferents
110
What mediates autonomic reflexes?
The spinal cord - also receives sensory afferent and brainstem input Brainstem nuclei - mediate autonomic reflexes Forebrain - cortical control could cause autonomic output e.g. anxiety Visceral afferents - sensory from organs takes priority over cortical e.g. needing the toilet badly
111
What does the hypothalamus do?
Feeding Thermoregulation Circadian rhythms Water balance Sex drive Reproduction
112
What are the principle transmitters in the ANS and where do they act?
Acetylcholine and NA They act on nAChRs, mAChRs, alpha and beta adrenoceptors
113
How are cAMP and protein kinase A levels changed?
Gas - stimulates 1) stims adenylyl cyclase 2) This increases cAMP 3) This increases PKA Gai - inhibits 1) inhibits adenylyl cyclase 2) lower cAMP 3) lower PKA
114
What is Gaq?
Part of g protein It increases phospholipase C - increases IP3 + DAG - this increases calcium levels
115
What are the different g proteins?
Gs, Gi, Gq They are g proteins Gs - alpha - activated adenylyl cyclase Gi - alpha - inhibits adenylyl cyclase - betadelta - activates k+ Gq - activates PLC - increase calcium
116
What are cholinergic receptors?
- Nicotinic - agonists = nicotine, antagonist = curare - Muscarinic - agonists = muscarine, antagonist = atropine Both have ACh as agonist
117
What are the mAChR subtypes?
M1, M3, M5 - These have Gq -> increased PLC - Increased calcium M2, M4 - These have Gi - inhibits adenylyl cyclase
118
Where are the different mAChRs found?
M1 = autonomic ganglia, glands, cerebral cortex - allows for gastric secretion and CNS excitation M2 = atria, CNS - cardiac and neural inhibition M3 = exocrine glands, smooth muscle, blood vessels - gastric and salivary secretion, GI SM contraction, vasodilation, eye accomodation M4 = CNS - enhanced locomotion M5 = substantia nigra, salivary glands - not known
119
How does our heart rate decrease?
Parasympathetic stimulation activated M2 receptors in atria - betadelta subunit will open k+ channels - moves out - more negative - decreases HR - slow AV conduction - decrease atria force
120
What do M1 and M3 do?
Gq coupled - contract smooth muscle (bronchoconstriction, GI motility, bladder voiding) Stimulate secretion from glands (mucus, lacrimal glands, salivary, sweat)
121
What effect would muscarine have?
low BP, high saliva, high tear flow, high sweat, nausea overdose: death from cardiac and resp failure
122
What effect would atropine have?
Inhibit secretion of saliva, tears, sweat ect. Relax smooth muscle Dilate pupils Increase heart rate
123
What's the name for drugs that indirectly enhance cholinergic transmission?
Cholinomimetic Inhibit acetylcholinesterase Anticholinesterase drugs: 1) long acting (irreversible) 2) nerve gas (organophosphates, pesticide)
124
What are noradrenaline and adrenaline receptors?
On tissues responding to postganglionic sympathetic neurons Beta - All Gas - all increase cAMP
125
What adrenaline receptor effects the heart?
NA (sympathetic neurones), A (chromaffin cells) bind to B1 receptors on ventricles and nodes 1) binds 2) stims adenylyl cyclase - more cAMP and PKA 3) This phophorylates calcium channels 4) calcium enter - contraction
126
What causes SM relaxation in bronchioles?
B2 activation - Gas activation - stims adenylyl cyclase - more cAMP, more PKA - phosphorylates SM
127
What are clinical uses of adrenoceptor agonists?
Adrenaline - cardiac arrest & anaphylaxis B2 selective - bronchodilator (salbutamol)
128
What are clinical uses of adrenoreceptor antagonists?
Can treat hypertension, heart failure, anxiety But can cause bronchocontriction and cardiac depression
129
What germ layers do epithelia develop from?
Endoderm (GI lining) Mesoderm (CV lining) Ectoderm (Epidermis) - in every organ
130
What are the functions of epithelia?
- protection - skin - absorption - SI - barrier - BBB - diffusion - lung - secretion - gland
131
What are the common properties of epithelia?
- can import or expel substances - have tight junctions - have apical (faces external environment) and basolateral domains with differing membrane properties (polarised)
132
Are epithelia cellular?
Entirely! - avascular (no blood vessels) - lack extracellular fibres - little extracellular space
133
Are epithelia polar?
Yes! There are differences between the apical and basal membranes (both specialised in different ways)
134
What is the basement membrane?
Separates cells from underlying connective tissue (collagen IV). ECM proteins secreted by epithelial cells: collagens, laminins, proteoglycans Structural support - basal lamina, reticular lamina (anchors BM to connective tissue below)
135
What are tight junctions?
Impede paracellular (between cells) movement Protein strands (claudins) determine tightness - 24 claudin genes Have high barrier function e.g. renal thick ascending limb Are leaky e.g. proximal tubule Variation in the permeability
136
What are adhering junctions?
Form belt around cell - under tight junctions - linked actin and cadherins Disruption can cause spread of cancer (metastasis)
137
What regulates epithelia?
- underlying mesenchymal cells form epithelium as cadherins change expression - this is epithelial-mesenchymal transition (EMT) - used for embryonic development and cancer metastasis
138
What are gap junctions?
Lateral communication between cells - allows small molecule diffusion between cytoplasms - cells electrically coupled
139
What are the junctional complexes of epithelia?
- Tight junctions - Adhering junctions - Gap junctions - Desmosomes
140
What are desmosomes?
Strong adhesion - has extracellular domains (cadherin). Anchor proteins (plaques) link cadherin domains to intermediate filaments There are some myosin filament interactions - contract
141
What links epithelia to basement membrane?
Actin-linked cell matrix junction Hemidesmosome
142
How are epithelial cells replaced?
From stem cells - tissue homeostasis Intestines - 5 days Lungs - 6 months
143
What are the four types of epithelia?
Simple - single layer Stratified - many layers (skin) Pseudostratified - upper resp Transitional - urothelium
144
What are the simple epithelia?
Simple squamous - thin, allow rapid passage Simple cuboidal - secretion/absorption of molecules by active transport - some have cilium
145
What is simple columnar and pseudostratified?
Simple columnar: may have cilia/microvilli, majority of GI tract, in fallopian tubes, in some respiratory Pseudostratified: single layer but looks like more, can be ciliated - these have goblet cells
146
What are the stratified epithelia?
Stratified squamous: most common stratified, in areas of abrasion Stratified cuboidal: less common, glands
147
What epithelia can change shape?
Stratified columnar: rare - in pharynx, anus, male urethra, embryo Transitional: round cells when relaxed
148
What secretes mucus, sebum and protein?
Mucus: mucus glands Protein: serous glands e.g. salivary Sebum: sebaceous glands e.g. oils on face
149
What are skeletal muscles responsible for?
- voluntary movement of bones - control of inspiration by diaphragm - skeletal-muscle-pump - returns venous blood
150
What is the skeletal muscle structure?
Striated Myofilaments - myofibril - muscle fibre - fascicle T tubules and sarcoplasmic reticulum form triad H and I change shape A doesn't
151
What causes skeletal muscle contraction?
ACh at neuromuscular junction - action potential in membrane of muscle Wave of depolarisation through t-tubule to interior of cell - runs near 2 areas of SR - triad Reaches sarcoplasmic reticulum Increase of intracellular calcium
152
What are the steps in cross-bridge formation and sarcomere contraction?
1) ATP binds to myosin head - dissociation of actin-myosin complex 2) ATP is hydrolysed - returns to resting state 3) crossbridge forms - myosin head binds to actin 4) Pi released 5) change in myosin - power stroke - filaments slide 6) ADP released 5 times a second
153
How many myosin heads in a thick filament?
~ 300 heads each head cycles 5x a second
154
What are the 3 types of muscle fibers?
Type 1 (slow oxidative) - non fatigue, red, low glycogen, high mitochondria e.g. soleus Type IIa (fast oxidative) - non fatigue, red, some glycogen, higher mitochondria e.g. gastrocnemius Type IIb (fast glycolytic) - fatigable, white, high glycogen, anaerobic, few mitochondria e.g. biceps
155
What are slow and fast fibres?
Slow - half the diameter and take longer to contract Fast - take 10 msec or less
156
What is muscle twitch?
Involuntary contraction - in three phases: latent - contraction - relaxation
157
What is isometric and isotonic contraction?
Isometric - muscle at fixed length - tension generated e.g. plank Isotonic - muscle stimulation causes a change in length e.g. bicep curl
158
What is botulinum toxin?
Linked to food poisoning - muscle weakness, paralysis - endoproteinase which cleaves exocytosis of ACh can be used for cross-eyedness (strabismum), uncontrolled eye movements (blepharospasm), and botox ADD TOXINS FOR ALL CHANNELS
159
What is the integumentary system?
- skin - largest organ - 12-15% of body weight - layers by 4 months in utero, 3rd trimester skin hardens (pigment absorbs light, blood and fat scatters light)
160
What are the layers of the skin?
Epidermis (epithelia) Dermis Hypodermis (adipose tissue)
161
What is the dermis?
2mm in soles/ 0.2 mm in eyelid Fibroblasts produce ECM proteins: collagen, laminin/fibronectin 2 zones: - papillary - thin loose connective tissue, motibility of leukocytes, mast cells and macrophages - reticular - thick dense irregular - adipocyte clusters Has all accessory organs: hair, nail, sweat glands Rich layer of blood, nerve endings and lymphatic vessels
162
What is the dermal-epidermal boundary?
Wavy boundary - dermal papillae (raised areas e.g. fingerprint), epidermal ridges The papillae facilitate nerve fibres reaching close to the surface
163
What is the epithelia in the epidermis of the skin?
keratinised stratified squamous epithelium
164
What are the layers of the epidermis?
Stratum corneum lucidum - stress protect granulosum spinosum basale Thin doesn't have lucidum - thick does No blood vessels Self-regeneration
165
What is the stratum basale?
Has keratinocytes - in touch with basement membrane (stem cells) Melanocytes give skin colour Merkel/tactile cells connected to sensory nerves
166
What are melanocytes?
Release melanin - UV absorb, antioxidant pheomelanin - red/yellow eumelanin - brown/black Pigment of skin = melanin + carotine (in fat + corneum) + blood Form melanosomes which are phagocytosed by keratinocytes
167
What is the stratum spinosum?
Several keratinocyte layers - usually thickest (unless thick skin - corneum) Produce keratin filaments - keratinocytes are linked by desmosomes so water retention Dendritic cells present
168
What is the stratum granulosum?
3-5 layers of flat keratinocytes Have dark staining granules Cells undergo apoptosis Produce glycolipid-filled vesicles which produce barrier between stratum spinosum
169
What is the stratum corneum?
Most superficial 15-30 layers of flattened corneocytes (dead keratinocytes) - stratum disjunctum: have corneodesmosomes which regulate desquamation - stratum compactum have a cornified envelope full of keratins - enclosed within proteins and surrounded by lipid envelope
170
What are nails?
Derivative of stratum corneum Packed with keratin New cells added in nail matrix Iron deficiency = fat/concave Hypoxemia = clubbed
171
What is hair?
Filament of keratinised cells from follicle. Hair bulb - in dermal papilla - hair matrix above Lanugo (soft hair) - vellus - terminal medulla - loose cells cortex - keratinised cuboidal cells cuticle - surface scaly cells
172
What are the 5 skin glands?
Eccrine/merocrine sweat glands - watery perspiration, controlled by SNS, temp regulation Apocrine sweat glands - cells pinch off and released into scent follicles - respond to stress and sex - armpits and gentials Holocrine sebaceous glands - cell disintegrates - oily skin and hair Ceruminous glands - e.g. earwax Mammary glands
173
How is skin a barrier?
Physical - keratin scaffold Biochemical - mild acidic, sebaceous glands (FAs inhibit bacteria, C6H) Immunological - dermal and epidermal langerhans cells
174
What are epidermal langerhans cells?
Immunological barrier - process antigens
175
How does vitamin D synthesis work?
Fat soluble - increases intestine absorption of Calcium Previtamin D3 in the keratinocytes is photolysed by UV acts via a nuclear receptor prohormone - first step Photochemical reaction
176
How does skin help with thermoregulation?
Anterior hypothalamus senses body temp Receptors Insulation Sweating Vasodilation/constriction There are arteriovenous anastomoses - have sympathetic innervation - low temp - increase innervation ect.
177
What is cardiac muscle?
Striated - branched with intercalated disks There are electrical coupling between myocytes by gap junctions
178
What is smooth muscle?
Involved in mechanical control of organ systems Non-striated - multiple actin fibres join at dense bodies Can be multiunit or unitary
179
How is calcium increased in skeletal muscles?
Depolarisation activates L-type calcium channels in T-tubule membrane - influx of calcium There's a mechanical tethering between the L-type channels in t-tubules and Ca channels (Ryanodine receptors) in sarcoplasmic reticulum - they open
180
Does cardiac muscle have t-tubules?
Yes! but only one branch of t-tubule is near SR (no triad)- dyad at the Z line No mechanical interaction between t-tubule receptors and ryanodine receptors The calcium instead triggers the receptors on the SR Calcium induced calcium release
181
How is calcium removed from muscle cells?
1) across the membrane by plasma membrane calcium ATPase (PMCA) or Na/Ca exchanger 2) back into SR via calcium ATPase
182
How do we increase calcium in smooth muscle?
No t-tubules, no triads or dyad - instead have shallow invaginations - caveolae Have two parts of SR - peripheral (next to caveolae) and central L-type ca channels still activate from action potential Activation of ryanodine receptors - calcium induced calcium Activation of Gq-coupled - IP3 production - IP3 receptors in SR (calcium channels)
183
What role does calcium have in cross-bridge formation?
Calcium binds to TnC - causes TnT to pull tropomysosin and TnI out of the way Myosin can now bind When calcium dissociates - everything goes back to normal
184
How does smooth muscle contract?
No troponin!! There's calponin and caldesmon instead. Calmodulin is stimulated by calcium Myosin light chain is phosphorylated by myosin light chain kinase - allows formation of crossbridge To stop - de-phosphorylate with MLCP
185
What is a motor unit?
Motor neuron and muscle fibres
186
What is the function of the circulatory system?
Primary - distribute gases Secondary: - fast chemical signalling - dissipation of heat - mediated inflammatory and host defences
187
What are the two types of circulation?
Left - systemic - Parallel pathway from left to right - Usually through single capillary bed - two in kidney ect. Right - pulmonary - single pathway from right to left
188
What does branching do for blood vessels?
Radius decreases with branching Combined cross-sectional area in daughter cells>parent cells CSA increase highest in capillaries
189
What are the layers in a blood vessel?
Endothelial cells -> elastic fibres -> collagen fibres -> smooth muscle cells Adventitia (outside) -> Media -> intima
190
What are the elastic arteries?
Large arteries - high compliance and can cope with high pressures
191
What are muscular arteries?
Medium sized - there are smooth muscle cells arranged circumferentially - can vasoconstrict and dilate
192
What are arterioles?
Connect to capillaries - have precapillary sphincters which monitor blood flow also have terminal regions - metarterioles smooth muscle regulated flow - regulated microcirculation
193
What are venules?
Are porous - exchange nutrients and waste - excellent reservoirs - have thin smooth muscle
194
What are capillaries?
Only endothelial and basement membrane - exchange gases, water, nutrients and waste Three groups: - fenestrated - continuous - sinusoidal (discontinuous)
195
What is starling's forces?
Fluid transfer in capillaries Jv = Kf [(Pc-Pi) - (Pi c - Pi i) + = filtration, - = absorption Jv = fluid movement Kf = hydraulic conductance Pc/i = Capillary/intestinal hydrostatic Pi = oncotic Pc declines down the capillary
196
What is the lymphatic system?
Drains excess interstitial fluid Maintains blood volume Transports dietary lipids Immunology
197
How are valves attached to the heart?
AV (mitral + tricuspid) connected by chordae tendinae and papillary muscles
198
What is in the heart wall?
Epicardium, myocardium (have cells connected by intercalated disks) and endocardium - all electrically active - have conducting (spread AP) and contractile (contract due to AP) cells
199
What is the myocardial cell structure?
Has gap junctions - allows current to flow Desmosomes anchor fibres together Undergoes excitation-contraction coupling
200
What is the cardiac cycle?
Depolarisation starts at SAN - spreads to AVN by gap junctions or conducting pathways. There's an AV ring - prevents spread to ventricle then carried to ventricle muscle
201
What is the cardiac cycle sequence?
1) Atrial systole - atrial depolarisation (contracts) - v fill 2) Isovolumetric ventricular contraction (mitral & tricuspid close) 3) Rapid ventricular ejection - semi lunar valves open 4) Reduced ventricular ejection - ventricle repolarisation 5) Isovolumetric ventricular relaxation - SLV close 6) Ventricular filling LOOK AT GRAPH
202
What ions are involved in the cardiac cycle?
Na+ = depolarise Ca+ = contracts myocytes K+ = repolarises Pacemaker current
203
What is an ECG?
Electrodes detect currents from different angles of the heart
204
What's on an electrocardiograph?
P wave = atria depolarisation QRS = ventricular depolarisation T wave = ventricular repolarisation
205
What is the BP like in arteries?
Arteries - high pressure, have low compliance, volume = stressed volume
206
What is the blood pressure in arterioles?
Has tonically active smooth muscle Have highest resistance to blood which is effected by: - sympathetic nerves (increases resistance) - alpha receptors = contract skin ect., beta = relax skeletal muscle and heart arterioles - need a balance - catecholamines e.g. adrenaline - vasoactive substances e.g. NO
207
What is the blood pressure in capillaries?
Low pressure - controlled by diameter of arterioles
208
What is the blood pressure in venules/veins?
Low pressure Has less elastic than arteries Has largest percentage of blood in CV - unstressed volume Large capacitance Has symp nerve fibres in smooth muscle + alpha adrenergic receptors - reduced capacitance - decreased unstressed volume
209
What is the velocity of blood in vessels?
V = Q/A Q - flow (mL/s) A - cross sectional area (cm) Small vessels have higher velocity
210
What is the blood flow equation?
Q (mL/s) = pressure difference (mmHg)/resistance
211
What is resistance to blood flow?
R = 8nl/pi x r^4 n = viscocity l = length of blood vessel Directly proportional to length and viscosity Inversely proportional to fourth power of radius Series resistance = within an organ: artery-arteriole-capillary ect. Arterioles have largest decrease Parallel resistance - branches - no loss of pressure
212
What pressures are in systemic circulation?
Arterial (Pa) - oscillations reflect diastolic and systolic pressure Venous (Pv) - by veins and venules (less than 10mmHg) Pulmonary circulation has lower pressure Greatest pressure drop in arterioles
213
What is pulse pressure and mean arterial pressure?
PP = systolic - diastolic pressure MAP = diastolic + 1/3 pp
214
How do we regulate BP?
Baroreceptors - in carotid and aortic sinuses Solitary sinus receives signal and directs SNS and PNS changes via medullar CV centres PNS --> vagus nerve --> SAN SNS --> SAN --> arteriole vasoconstrict --> vein vasoconstrict --> cardiac muscle contracts more There's also chemoreceptors - increase BP if low O2 (low pH)
215
What is a long term control of BP?
RAAS: low perfusion in kidney - renin released - converts angiotensinogen to angiotensin I to II. Angiotensin II increases aldosterone - increases Na and releases ADH - more water - also vasoconstricts arterioles
216
What does chronic hypertension do?
Desensitise baroreceptors - reduces stretch sensitivity - reduced sympathetic inhibition - hypertention not corrected people here don't usually experience a dip in BP at night - higher risk of heart attack ect. Can be treated by lifestyle changes, ACE inhibitors, Ca channel blockers, diuretics, beta blockers
217
What is in blood?
Cellular components in plasma - erythrocytes - leukocytes - platelets
218
What is in plasma?
Albumin Fibrinogen - precursor of fibrin Immunoglobulins Proteins in coagulation cascade
219
What are erythrocytes?
Most abundant non-nucleated biconcave disks 3 main functions: co2/o2 carriage, buffering
220
What are the white blood cells?
Granulocytes: neutrophils (phagocyte) eosinophils (combat viruses and parasites) basophils (release histamines ect.) Non-granular: lymphocytes (mature into B and T) monocytes (macrophages and dendritic)
221
What are platelets?
Bud off megakaryocytes in bone marrow - thrombopoesis in response to thrombopoetin and IL-3 1) Platelets bind to TPO 2) megakaryocytes not generated 3) If no platelets bind to TPO (as little platelets) - TPO stimulates megakaryocytes and platelets 150000 - 450000 in blood
222
What is haemostasis?
Prevention of a haemorrhage 1) vasoconstriction (serotonin, thrombin ect.) 2) Increased tissue pressure 3) platelet plug (primary haemostasis) 4) clot formation (secondary haemostasis)
223
What is the structure of a platelet?
No nucleus - have mitochondria, lysosomes, peroxisomes, alpha granules (VWF, fibrinogen, clotting factor, platelet derived growth factor), dense factors (ATP, Ca) Have lots of receptors Tubulin helps maintain shape Cytoskeleton has actin and myosin
224
What are the three parts of a platelet plug formation?
1) platelet adhesion 2) platelet activation 3) platelet aggregation
225
What is platelet adhesion?
Exposed endothelium exposes collagen - VWF binds to collagen and platelet receptors Endothelial cells also release VWF Binding cause IC cascade - activate
226
What is platelet activation?
Cascade causes: - secretion/exocytosis of dense and alpha granules (VWF and ADP - both activate it further) PDGF - wound healing Thromboxane - vasoconstrict and inflammation Cytoskeleton changes Expression of fibrinogen receptors
227
What is platelet aggregation?
Fibrinogen binds to platelet receptors - forms bridges between platelets - this plugs the break in endothelium Eventually actin and myosin contract - stronger plug
228
What is a blood clot?
More permanent fibrin mesh Mass of erythrocytes, leukocytes, serum and the mesh already there Thrombus = intravascular clot
229
What is the intrinsic and extrinsic pathways in clotting?
Intrinsic (slow) - factors in blood contact with negatively charged membrane of platelet - causes cascade of protease reactions - ends in factor Xa Extrinsic - endothelium injury causes tissue factor (receptor) to become activated when in contact with factor VII - results in factor Xa xa from both enter common pathway - generates thrombin - produces fibrin
230
What prevents haemostasis?
Normal endothelial cells - through paracrine and anticoagulant factors Paracrine factors - e.g. prostacyclin promotes vasodilation - inhibits platelet steps Many anticoagulant factors - some stop thrombin Promotion of pro-thrombotic state via vascular damage and hypoxia Turbulent flow causes endothelial injury - caused by stenosis, large radius and high velocity
231
What are virchow triad's risk factors?
Thrombosis: Abnormal blood flow Endothelial injury Hypercoagulability
232
How much Na+ and water is excreted through our urine?
water - 1.5L per day in urine (1.1 by respiration, stools and sweat) Na+ - 140 mmoles per day in urine (10mmoles in stool and sweat)
233
What is the anatomy of the kidney?
from T12 to L3 - around 10cm long and 5.5cm wide Capsule Cortex Medullary ray Pelvis Ureter
233
What are the two types of the nephron?
Superficial nephron (85%) in the cortex Juxtamedullary nephron - 15%
234
What are some congenital abnormalities in the kidney?
Ectopic kidney Horseshoe kidney - fused Renal agenesis - lack/failure to develop
235
What is renal failure?
Fall in GFR (usually 125ml/minute) - increase in serum urea and creatinine Can be: - acute (reversible) - chronic (irreversible)
236
What are the differences between acute and chronic renal failure?
Chronic has longer history Haemoglobin level lower in chronic Renal size lower in chronic Chronic has peripheral neuropathy
237
What is renal failure progression?
Thickening glomerular membrane --> damaged glomeuli --> scarring --> reduced renal size
238
What is uraemia?
Describes the symptoms of renal failure - hypertension - nausea - anaemia - bone diseases - neuropathy ect.
239
What happens at each stage of renal failure?
As the stages progress - GFR decreases Uraemic syndrome becomes more severe Serum biochemistry gets severe Begins with anaemia and bone disease -- dialysis
240
What causes renal failure?
30% - glomerulonephritus 25% - diabetes 10% - hypertension
241
What does the lymphatic system do?
Drain excess interstitial fluid and return to blood via subclavian vein to maintain blood volume
242
What features of a cardiac cell enable the heart to beat?
Gap junctions Intercalated disks Sarcolemma T tubules Desmosomes
243
What is the first step in producing urine?
Glomerulus (200 micrometers) - ultrafiltration - 180 litres daily GFR = 125 ml/min Filtration - allows H2O and other molecules Ultrafiltrate - protein free plasma
244
What is the second step of producing urine?
Filtrate modification There is reabsorption in PCT and secretion from the blood in the tubules
245
What are the types of tubular transport?
Transcellular reabsorption Transcellular secretion Paracellular secretion and reabsorption
246
How are genes related to nephron transport?
Produce transport proteins
247
What happens at the proximal tubule?
Bulk reabsorption (70%) - 70% water and sodium - 100% glucose and amino acids 90% bicarb Sodium pumped out basally by Na/K pump - Na and glucose/phosphate(NaPiIIa)/aa then cotransport into the cell apically - water then diffuses paracellularly
248
What is the NaPiIIa knockout mouse?
- caused less Pi reabsorption - more lost in urine - issues in renal mineralisation - more stones - increased calcification
249
What is NHE3 in proximal tubule?
Bicarb reabsorption - NHE3 removes H+ (which reacts with bicarb apically - makes h2O and CO2 which can move in an dissociates back to bicarb and H+) and allows Na to move in - Na then leaves and takes bicarb into blood Knockout mice: - lower pH as bicarb falls - inhibits H+ secretion, Na/HCO3- transport
250
What is secreted by PCT?
Foreign compounds e.g. penicillin Removal of plasma proteins bound substances
251
What happens in the loop of henle?
Concentration of urine Reabsorption of Na, Cl and water Reabsorption of Ca and Mg Site of action of loop diuretics
252
What are the limbs in the loop of henle?
Thin descending - H2O moves out Thick/thin ascending - Na/Cl moves out
253
Which channels move Sodium and Chlorine out of the thick ascending limb of the LOH?
NKCC2 moves sodium, 2 chlorine and a potassium into the cell Sodium potassium pump - pumps sodium out CLCK - move Cl out basolaterally ROMK - move k+ out apically Calcium and magnesium move paracellularly
254
What is bartter's syndrome?
Recessive - 1 in 1 million Causes mutations in NKCC2, CLCK and ROMK - loop of henle - Cl accumulates, type 1 = NKCC2 mutations Causes hypotension Salt wasting Hypokalaemia Alkalosis Hypercalciuria - high calcium in urine Polyuria
255
What are loop diuretics?
Furosemide Bumetanide Effects NKCC2 - treats high blood pressure - has bartter's like symptoms
256
What is the early DT?
Early distal tubule - reabsorption of Na and Cl - reabsorption of Mg - sensitive to thiazide diuretics
257
What channels are involved in the early distal tubule?
NCC - cotransports Na/Cl into cell Na/K pump - pumps sodium out basolaterally CLCK - pumps calcium out basolaterally Mg and Ca enter through channels Thiazide stops NCC - treats high BP - has Gitelman's symptoms
258
What is Gitelman's syndrome?
Recessive - 1 in 40,000 - 1 in 1000 in Asian populations, 1% of Caucasian are carriers Affects NCC in distal tubule - salt wasting - hypotension - hypokalaemia - metabolic alkalosis - hypocalciuria - low calcium in urine
259
How can we see the impact of mutations on Na+ transport?
Xenopus oocyte expression studies - inject RNA - protein made - evaluate if the channel is made
260
What does it mean if you carry a mutation for ROMK, NCC or NKCC2?
Protection from hypertension
261
What are some NMJ inhibitors?
- K+ - dendrotoxin - ACh release - botulinum toxin, tetanus toxin - Ca2+ - w-conotoxin - Neuronal Na+ - tetrodotoxin, saxitoxin - Acetylcholinesterase - physostigmine, DFP - Muscle Na+ - tetrodotoxin, saxitoxin - AChR channel - a-bungarotoxin, d-tubocurarine
262
What do the late distal T, collecting T and the cortical collecting duct do?
Concentration of urine Reabsorb Na and H2O Secrete K and H
263
What cells are in the late DT and cortical collecting duct?
Principal: reabsorb Na and H2O secrete K and H+ Intercalated: - alpha - H+ secretion, bicarb reabsorption - beta - H+ and Cl- reabsorption, bicarb secretion
264
What channels does the principal cells have?
ENAC - allows Na to enter cell apically ROMK - allows K+ to leave apically Aquaporin 2 - allows water in apically Sodium/potassium channel - allows sodium to leave basolaterally Kir2.3 - allows K+ to leave basolaterally Aquaporin3/4 - allow water to leave basolaterally
265
What does amiloride do?
Stops ENaC in a principal cell - no Na+ can be reabsorbed Used for Liddle's syndrome - reduces blood pressure
266
What is liddle's syndrome?
Autosomal dominant - ENaC isn't removed - more Na Na+ retention - fluid retention Hypertension Hypokalaemia Metabolic alkalosis Low renin and aldosterone
267
What is ENaC like in Liddle's syndrome?
COOH tail in beta or gamma subunit is mutated Proline is deleted - there is a reduced removal of ENaC Therefore more ENaC - more Na leaves - more water reabsorbed - causes hypertension (MAP = CO x HR) Also means more K+ secretion - hypokalaemia
268
What channels are in alpha intercalated cells in late DT and CCD?
Proton pump apically - pumps H+ out AE1 exchanges a bicarb out basally, brings in Cl- Cl- exits basally
269
What channels are in beta intercalated cells in late DT and CCD?
AE1 - bicarb out apically, Cl- into cell Proton pump - pumps H+ out basally Cl- leaves basally
270
What is the medullary collecting duct?
Low Na+ permeability High urea and H2O permeability in presence of ADH
271
What happens when someone has acute renal failure?
Fall in GFR Impaired fluid and electrolyte homeostasis Accumulation of nitrogenous waste Needs dialysis
272
What are the symptoms of acute renal failure?
Hypervolaemia Hyperkalaemia Acidosis High urea and creatinine
273
What is the fall in GFR called?
Oliguria - due to hypotension - pre-renal cause Treated by IV saline, add HCO3-
274
Where does most Na reabsorption happen?
PCT - 70% Loop - 20% DT and CD - 9% - by aldosterone
275
Where does most H2O reabsorption happen?
PT - 70% Loop - 5% DT and CD - 24% - by ADH
276
Where does most K+ get reabsorbed?
PT - 80% Loop - 20% DT and CD - only in aldosterone
277
How is the SA node innervated?
By vagus nerve (parasymp) - depresses heart rate - this is called negative chronotropic action and is mediated by M2 acetylcholine receptors Symp - catecholamines increase HR by activating B1 adrenoreceptors - increases cAMP - PKA activation - activates L-type Ca channels and Ca channels on ER
278
What did Otto Loewi see with the frog heart?
He collected the fluid bathing heart and applied it on a different heart - it slowed - this meant that it was a chemical, not electrical, released from vagus nerve
279
What is the Langendorff preparation?
1) Anesthetise the animal 2) Cut open chest and remove heart 3) Place heart in dish of warm Ringer's solution - press on heart slightly to remove any blood 4) Tie aorta to cannula and perfuse with warmed, aerated Ringer's solution - this perfuses the coronary arteries 5) Place in water jacket to keep heart warm 6) attach hook to apex of ventricles and connect to force transducer - allows us to convert physical movement to electrical signal
280
Where is ADH produced?
Supra-optic and paraventricular nuclei
281
What are the hypothalamic osmoreceptors?
Supra-optic and paraventricular nuclei detect a change of 3 mosmol/Kg of H2O (normal range is 280-300) Causes release of ADH and thirst - at normal osmolality there is still ADH in the plasma
282
What affects the release of ADH?
Increase: water deficiency, stress, drugs (nicotine and ecstasy) Decrease: excessive fluid, drugs (alcohol)
283
What does ADH do in principle cells?
ADH binds to a V2 receptor which causes insertion of AQP2 channels by activating PKA to stimulate vesicles - dilutes plasma - increases H2O reabsorption - fall in body osmolality - fast (~ 15 minutes)
284
What is diabetes insipidus?
Lots of dilute urine - we can use a desmopressin nasal spray to stop ADH release - we can defect the V2/AQP2 channels
285
What does aldosterone do?
Released from adrenal cortex - zona glomerulosa (mineralcorti) Regulates (increases) Na, K and body fluid volume Released in response to high K, low Na or low volume Acts on late distal/cortical and medullary collecting duct
286
How does aldosterone act on principle cells?
1) binds to cytosolic mineralcorticoid receptor 2) transport to nucleus 3) increases expression of transport proteins 4) There will be Na reabsorption and K/H+ secretion Can take a few hours Na comes in via Na/H exchanger - goes to blood by Na/K pump - K leaves apically
287
What does aldosterone do to alpha intercalated cells?
1) binds to cytosolic mineralocorticoid receptor 2) transports to nucleus 3) increases transcription of protein transport channels 4) H+ is secreted
288
What is pseudohypoaldosteronism?
There is Na loss but high aldosterone - loss response There are mutations in mineralocorticoid receptor mutations
289
What does renin-angiotensin regulate?
Body fluid volume, plasma Na and K+
290
What is RAAS?
Renin released from the juxtaglomerular apparatus Renin causes angiotensinogen to be converted to angiotensin 1 ACE1 (from lungs) causes angiotensin I to convert to angiotensin II
291
What does angiotensin II do?
Causes zona glomerulosa to release aldosterone Vasoconstricts arterioles - increase BP ACE inhibitor - BP treatment
292
What are the two types of respiration?
Internal - within the cell External - ventilation, gas exchange
293
What are the different parts of the respiratory system?
External convection Pulmonary diffusion Internal convection Tissue diffusion
294
What are the branches of the lungs?
Trachea --> bronchi --> bronchioles (terminal and respiratory) --> alveoli (from terminal bronchiole) Conducting zone - air travel Respiratory zone - air diffusion
295
What is the conducting zone?
Nose, nasopharynx, oropharynx, pharynx, larynx, trachea, bronchial tree - filters, warms and humidifies air
296
What is the structure of the bronchial wall?
Cartilage Smooth muscle Elastic tissue Mucous glands
297
What is respiratory epithelium?
Ciliated epithelia Goblet cells Sensory nerve endings
298
What is the structure of bronchioles?
Lack of cartilage Has respiratory epithelium Has more smooth muscle than bronchi proportionally
299
What is the air blood barrier?
Created by flattened cytoplasm of type I pneumocyte and capillary wall
300
What is quiet inspiration?
Involves primary muscles: diaphragm and external intercostals - follows Boyle's law: pressure volume relationship
301
What is forced inspiration?
Uses primary muscles (diaphragm and external intercostals) and accessory (sternocleidomastoid, scalenes, back and neck) muscles
302
What is quiet expiration?
Passive - due to elastic recoil
303
What is forced expiration?
Uses accessory muscles, internal intercostals, abdominal muscles and neck and back muscles
304
What is the pleura?
Pleural cavity - prevents lungs from sticking to wall or collapsing - allows free expansion Parietal is the outside Visceral is the inside
305
What is pneumothorax?
Collapsed lung
306
What is compliance?
= distensibility c = change in volume/change in pressure low compliance = more work to inspire e.g. pulmonary fibrosis high compliance = more work expiring (less elastic recoil) e.g. emphysema
307
What are the components of elastic recoil?
Anatomical - elastic nature and extracellular matrix Surface tension = due to differences in forces, there's a balance between pressure and surface tension
308
What is Laplace's law?
Pressure = 2(tension)/radius
309
What is surfactant?
Produced by type II pneumocytes - prevents alveoli collapsing and reduces surface tension
310
What is dead space?
Anatomical - volume of conducting airways Physiological - volume of lungs not participating in gas exchange - conducting zone + non-functional respiratory zone
311
What are some spirography values?
IRV - inspiratory reserve volume (maximum inspiration - tidal volume) FRC - functional residual capacity During exercise - changes Can't measure RV
312
What is Poiseuille's law?
Impact of resistance to flow R = (8/pi) x (viscocityXlength/radius ^4) R = 1/r^4
313
What is the normal airway resistance?
1.5 cm H2O.s.litres
314
What factors affect airway resistance?
Anything affecting airway diameter - increase mucus secretion - oedema - airway collapse
315
What controls bronchial smooth muscle?
Parasymp - ACh from vagus acts on MAChR - constricts Symp - noradrenaline causes dilation Adrenaline in blood - dilation Histamine - constriction
316
How can we calculate residual volume?
Breathing with a balloon with helium - gets diluted (measure conc before and after)
317
Is airflow proportional to pressure gradient?
yes! directly It is indirectly proportional to resistance
318
Where is most of the resistance in the airways?
Pharynx/larynx - 40% Airways>diameter 2mm - 40% Airways
319
What is the composition of air at 760mmHg?
Dry (atmospheric) - mostly nitrogen (78%), then oxygen (21%) Wet (trachea) - similar but has H2O Henry's law: [gas] = solubility coefficient x pp
320
What is Dalton's law?
The total pressure of a mixture of gases is the sum of their individual partial pressures
321
How can we work out the conc of a gas dissolved in a solution?
Using Henry's law: [Gas]dis = s (solubility coefficient) x Partial pressure of gas
322
How is oxygen transported?
O2 is has a low solubility in saline - 0.003 ml/100ml blood This is too little so haemoglobin is needed
323
What is haemoglobin's structure?
Tetrameric - 2 alpha and 2 beta Has a haem group and a globin chain Can be tensed (low O2 affinity) or relaxed (high O2 affinity)
324
What is the structure of the haem unit?
Porphyrin ring with an iron atom For O2 to bind, iron must be in state Fe2+ Methaemoglobin reductase converts Fe3+ to Fe2+ Haemoglobin can be relaxed or tensed
325
What is the oxygen-haemoglobin dissociation curve?
X axis = pp of O2 Y axis = haemoglobin saturation Increases then plateaus At high temp = carries less, low temp = carry more At high pH = carries more, low pH = carries less - BOHR EFFECT At high 2,3 diphosphoglycerate conc = carries less, at low conc = carries more
326
What causes a right shift in the oxygen-haemoglobin curve?
- increased temp - increased CO2 production - decreased pH
327
What is fetal haemoglobin?
Beta chains are replaced by y chains - left shift in curve - higher O2 affinity
328
How is CO2 transported in the blood?
CO2 + H2O <-> H2CO3 <-> HCO3- + H+ The blood can carry CO2 in many ways e.g. carbonic acid, bicarb, dissolved CO2 - grouped as total CO2
329
What is carbon transport?
CO2 is in plasma - can remain or enter RBC - 10% remains Remain - can dissolve, bind to plasma protein, some form bicarb (slow with no carbonic anhydrase) Entering the RBC - can cross by AQP1 or Rh protein or diffuse through bilayer Some dissolves in RBC fluid, some bind to haemoglobin (Hb-NH-COO-) doesn't bind to iron, rest is converted to bicarb by carbonic anhydrase - bicarb can leave by bicarb/Cl exchanger When at lungs - this is reversed
330
Why do we have a GI system?
Breaks down food into nutrients so we can use them for energy and growth& repair Eliminates waste and undigested food Helps regulate blood sugar, immune system, promote good mental health
331
What is the GI tract?
A muscular tube - intestines are suspended in the cavity by mesenteries Hollow organs are separated by sphincters Accessory organs secrete into the lumen Functions include: Motility propels food, digestion, absorption
332
What is the structure of the GI wall?
Mucosal layer: epithelia (villi), lamina propria (capillaries, enteric neurones, immune cells), thin muscularis mucosae Submucosal layer: connective tissue, glands, larger blood vessels Circular and longitudinal smooth muscle Serosa (squamous epithelia)
333
What is the mouth?
For mastication Has exocrine glands: lipase and amylase, saliva lubricates bolus, antimicrobial, buffers and dissolves food Sensory information is relayed to brainstem
334
What is the oesophagus?
Has stratified squamous epithelia Swallowing causes upper oesophageal sphincter to close - initiates peristaltic wave Continued distention = second peristaltic wave Vagovagal reflex controls lower oesophageal sphincter - PNS vagus does this
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How is the GI tract regulated?
By three divisions of ANS: - extrinsic = PS + S - intrinsic = ENS (primary) ENS has two main plexuses - ganglia in submucosal and myenteric plexuses, submucosal is between mucosa and circular muscle, myenteric is between circular and longitudinal Lots of neurones - >100 million
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How is the parasympathetic NS involved in the GI tract?
Ganglia in plexuses coordinate information to SM, endocrine and secretory cells Postganglionic neurones are either cholinergic (ACh) or peptidergic (peptides e.g. substance P)
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How is the sympathetic NS involved in the GI tract?
Postganglionic nerve fibres release noradrenaline - mixed efferent and afferent - relayed between GI tract and CNS
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What are the three phases to motility in the stomach?
1) receptive relaxation in thin-walled orad (fundus and some body) stomach 2) 3 layers of caudad region (body and atrium) contract to mix food with gastric juices from mucosal glans (ANS control) - makes chyme - HCl, Pepsinogen --> pepsin, intrinsic factor, mucus 3) gastric emptying through pyloric sphincter into duodenum - fat and H+ slow this
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What causes motility (GI)?
Subthreshold slow waves produce weak contraction (tonic) Action potentials on top (phasic contractions) Low pressure organs separated by sphincters (6 + sphincter of oddi) Regulate antegrade (forward) and retrograde (backward) movement
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What is the most contractile tissue?
Unitary smooth muscle - cells electrically coupled by gap junctions
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What are the types of GI contractions?
Tonic - constant level of contraction Phasic - periodic contraction then relaxation Contraction is preceded by electrical activity - cells of cajal
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What is the small intestine?
Digestion and absorption of nutrients - chyme is mixed with digestive enzymes and pancreatic secretions There are many hydrolytic enzymes in brush border Duodenum --> jejunum --> ileum SA increases - plicae - villi - microvilli
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What is the pancreas?
Secretes pancreatic juice (1L daily) into duodenum - rich in bicarb (by centroacinar and ductal cells) to neutralise H+ - enzymes secreted by acinar cells PNS secretes, SNS inhibits In cephalic phase - gastic and intestinal
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What are the GI accessory organs?
Pancreas, liver and gallbladder
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What does the liver and gall bladder do?
Hepatocytes secrete bile - gall bladder stores and ejects - CCK is released from SI when chyme enters which relaxes sphincter of oddi
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What is in bile?
Water Amphipathic bile salts (aids fat digestion) Bilirubin Cholesterol Phospholipid Electrolytes - Na, K, HCO - 95% bile salts recirculate to liver by enterohepatic circulation
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What are the contractions in the SI?
Peristaltic contractions propel chyme Segmentation contractions split and expose chyme to secretions - enterochromaffin cells release serotonin - peristaltic reflex Material not absorbed passes through ileocaecal sphincter into caecum of LI
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What regulates the GI system?
GI peptides: - hormones e.g. GIP - paracrines e.g. somatostatin - neurocrines - from neurone after action potential
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What are the functions of the large intestine?
1) absorbs water and electrolytes (aldosterone increases Na absorption) 2) makes and absorbs vitamins K + B 3) forms and propels faeces
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What is the LI structure?
Surface columnar epithelium - interspersed with crypts Has taenia coli - 3 longitudinal muscles and haustra Caecum and proximal colon mix contents
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What are the two types of lung disease?
Obstructive - reduced flow through airways Restrictive - reduced lung expansion Both reduce ventilation
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What is the flow-volume relationship?
Highest flow at low volume then gradual decreases Negative flow = flow out
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What is obstructive lung disease?
Narrowing airways Could be due to: - excess secretions - bronchoconstriction (asthma) - inflammation Increased resistance FEV1<80% FVC FVC is usually normal - FEV1 affected There is a sharp fall in flow-volume - graph isn't a straight line (normal) - looks like a banana
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What are some obstructive diseases?
Chronic bronchitis - persistant cough and mucus Asthma - inflammatory COPD Emphysema - loss of elastin
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What is asthma?
Hyper-active airways Trigger could be: - atopic (extrinsic) = allergies - non-atopic (intrinsic) = cold air, stress, exercise, drugs, irritants, resp infections Causes bronchoconstriction Short acting treatment = salbutamol (B2 adrenoreceptor agonist) Long acting treatment = inhaled glucocorticoid steroids or long acting B2 agonists
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What is restrictive lung disease?
Reduced chest expansion - chest wall abnormalities, muscle contraction deficiencies Loss of compliance - ageing, increased collagen, environment Vital capacity is reduced - FEV1 is the same Flow-volume graph tends to be normal
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What is asbestosis?
Slow build up of fibrous tissue leading to loss of compliance
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What are the two medullary centres?
Dorsal respiratory group - controls inspiration by sending signals to inspiratory muscles - spontaneously active Ventral respiratory group - controls inspiration and expiration - inactive during quiet respiration - helps when forceful
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What two centres are in the pons?
Pneumotaxic centre - increases breathing rate by shortening inspiration - inhibitory effect on inspiratory centre Apneustic centre - increases depth and reduces breathing rate by prolonging inspiration - stims inspiratory centre
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Can stretch receptors feedback for breathing?
Yes! Hering-Breuer reflex - stretch receptors in lungs send signals to medulla and limit inspiration and prevent over-inflation Phrenic nerve --> diaphragm --> lung stretch receptor --> vagus nerve --> inspiratory centre inhibited
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Can chemoreceptors feedback for breathing?
Yes! Central: monitor CSF CO2 and pH - if rise in CO2 - increase ventilation Peripheral: in carotid body and aortic arch - respond to increased CO2, decreased pH, decreased O2 - increases ventilation
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What is the pre-botzinger complex?
Provides breathing rhythm - pattern generator
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What is the secretion in the Gi tract?
Controlled by hormonal, paracrine and neurocrine control. >9L of fluid daily - most absorbed in SI - rest lost in LI or in faeces Salt and water balance regulates ECF volume and BP
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What is the secretion in the stomach?
Distal: gastrin, somatostatin, pepsinogens Proximal: HCl, pepsinogens, intrinsic factor, mucins, bicarb
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What is the stomach's main three functions?
Secretion Motor Humoral (gastrin, somatostatin)
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What are the stomach's secretory cells?
Mucosal layer Secrete >2L daily Body: oxyntic glands - epithelial cells (bicarb) - mucous neck cells (mucus) - Parietal cells (HCl, intrinsic factor) - enterochromaffin-like cells (histamine) Antrum: pyloric glands (same as pyloric but no parietal cells) - G cells (gastrin hormone) - Chief cells (pepsinogen) - enterochromaffin cells (serotonin, VIP, substance P) - D cells (Somatostatin)
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What do the stomach's secretions do?
Protective: - Bicarb - neutralises acid and combines with mucus to form a protective barrier - Mucus - protects epithelia Hydrolytic: - HCl - activated pepsinogen and denatures proteins - Pepsinogen - precursor of pepsin - digests protein Endocrine: - Gastrin - increases HCl secretion and pepsinnogen release- Intrinsic factor - B12 absorption Histamine - increases parietal cell HCl secretion Serotonin/VIP - motility and secretion, VIP decreases HCl Substance P - SM contract Somatostatin - inhibit gastrin release
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What is the parietal cell structure?
While resting: cytoplasmic pool of tubulovesicular membrane - contains acid secreting H,K-ATPase Stimulated: induces cytoskeletal changes - tubulovesicular and canalicular membranes fuse - increases SA by 50/100x, microvilli are present, insertion of H,K-ATPase pump, K+ + Cl- channels
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How is gastric acid secreted by parietal cells?
H2CO3 in the cell - H+ is secreted apically through H+/K+ ATPase Cl- follows out HCO3- absorbed into blood via Cl--bicarb exchanger There are Na/K+ exchangers basally Theres K+ channels allowing K+ to exit the cell apically
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What regulated HCl secretion?
Stimulation: ACh (Vagus), histamine (ECL) and gastrin (G cells) Inhibition: low pH, somatostatin, prostaglandins
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What is fluid and electrolyte absorption like along the intestine?
SI and LI have crypts of leiberkuhn - secrete fluid and electrolytes Si absorb fluid and Na/K/Cl/bicarb by villi, Li by surface epithelia Crypt epithelial cells - secrete fluid + electrolytes - protective LI - has a net absorption of water/ Na/ Cl, secretes bicarb and K SI - have plicae (folds of kerckring), villi and microvilli - increase SA by 600x Duodenum and jejunum is the primary site for Na/Cl/K/bicarb absorption
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How does secretion in the intestine happen?
In epithelial cell of crypts of leiberkuhn Na/K/Cl cotransporter brings ions into the cell from the blood Cl diffuses into the lumen through Cl channels - open when cAMP increases due to GPCR - open by ACh/VIP ect. Na follows paracellularly (passive) Water follows
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How does absorption happen in the jejunum?
All Na absorption - Na/K ATPase Low intracellular Na (by sodium potassium exchanger) drives entry via Na channels/ Na-H exchangers/ Na-glucose/aa cotransport - secondary active transport The Na/H exchangers are stimulated by bicarb Net absorption of NaHCO3
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How does absorption happen in the ileum?
Same as jejunum but also involves Cl Has a bicarb/Cl exchanger which brings Cl into the cell There is a Cl transporter - Cl absorbed Net NaCl into cell
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What happens in pancreatic secretion?
Acinar cells secrete CCK Bicarb secreted into pancreatic juice by Cl/bicarb exchanger H is transported into blood by NaH exchanger Net secretion of bicarb and H absorption Ductal cells - recs for CCK, ACh and secretin to upregulate production
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What is absorption in the large intestine?
Aldosterone causes Na to enter colon cell apically Na leaves into blood by Na/K ATPase This brings in potassium - leaves apically
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What products do the jejunum and ileum absorb?
Carbohydrases: alpha/beta amylase, maltase, sucrase, trehelase, lactase ---- into villus blood Protease: pepsin, trypsin, chymotrypsin, elastase, carboxypeptidases ---- into villus blood Lipases and bile salts ---- into lacteals in villus
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How does the SI absorb carbohydrates?
Epithelial cells SGLT1 - brings Na and Glucose/galactose in GLUT5 - brings fructose in GLUT2 - takes all sugars to blood Na/K pump basally
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How does the SI absorb protein?
Na brings in amino acids H brings in di/tripeptides - peptidases break them down in the cell A channel takes AAs into blood Theres a NA/H exchanger apically Na/K pump basally
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How are lipids absorbed?
Pancreatic lipase and other lipids hydrolyse by bile salts in duodenum and jejunum Products: cholestrol, lysophospholipids, monoglycerides, micelles (have amphipathic bile salts) In mucous gel layer epithelia - FAs become protonated and cross the enterocyte by diffusion, carrier mediated transport, incorporated into membrane Products are resterfied in SER - packaged into chylomicrons - absorbed into lacteals
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What are the islets of langerhan?
In kidneys Beta cells (65%) - insulin, pro insulin, C peptide, amylin Alpha cells (20%) - glucagon Delta cells (10%) - somatostatin There are also: F cells - pancreatic polypeptide e cells - ghrelin protein enterochrommafin cells - not in islets Richly perfused with blood
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What is the communication to the islets?
Small arteries enter islet - distribute by fenestrated capillaries Vascular arrangement
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How do the islets cells communicate to eachother?
Gap junctions between beta and alpha cells Delta cells send dendrite-like processes to beta cells
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What are the islets innervated by?
Adrenergic, cholinergic and peptidergic neurones
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How is insulin secretion regulated?
High blood glucose stimulates Symp stimulation: Beta-adrenergic increases secretion, alpha decreases Parasymp stimulation: vagus ACh increases release GIP (SI K cells), Amylin (beta cells) and somatostatin Drugs e.g. sulphonylureas act on KATP increasing insulin secretion
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How is insulin secreted?
GLUT2 lets glucose in - makes ATP from glycolysis ATP closes k+ channels - depolarisation Ca channels open causing exocytosis CCK acetylcholine - Gq coupled Somatostatin decreases, Glucagon and beta adrenergic agonists increases
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How does insulin act to a receptor?
Heterotetramer - alpha/beta subunits + IC tyrosine kinase Receptor activation activates or inhibits - PKC, phosphatases, phospholipases, G proteins Causes cell growth, division, gene expression High insulin levels --> receptor downregulation
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What is insulin's action?
Binds to receptor --> signal transduction cascade --> causes exocytosis of a vesicle with GLUT4 ---> allows glucose to enter Target all cells - especially muscle and liver to make glycogen - increases fat cell glucose intake when glycogen levels replenish
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How is the liver acted on by insulin?
Promotes glycogenesis Inhibits glycogenolysis Inhibits gluconeogenesis
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How does insulin effect muscle?
1) Promotes glucose uptake (GLUT4) 2) Promotes glycogen synthesis 3) Promotes glycolysis and carbohydrate oxidation 4) Promotes proteinsynthesis and inhibits protein breakdown
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How does insulin effect adipocytes?
Increases GLUT4 expression, converts glucose to FAs (stores as triglycerides), increases lipoprotein lipase - makes triglycerides from FAs, inhibits oxidation of fat Overall decreases levels of FAs and keto acids
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How does insulin cause satiety?
Promotes K+ uptake through Na/K ATPase This effects hypothalamic satiety centre
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What is type I diabetes?
This is where there is islet destruction - autoimmune There is hyperglycaemia and increased blood fatty acids and keto acids Hyperkalaemia Hypotension Polyuria Symptoms: hunger, increased thirst, weight loss, fatigue, fruity breath, blurred vision Treatment: insulin replacement therapy
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What is type II diabetes?
Insulin resistance Symptoms: increased thirst, hunger, urination, weight loss, headaches, tired, blurred vision Treatments: sulphonyurea drugs e.g. tolbutamide (stimulate insulin secretion), biguanide drugs e.g. metformin (upregulate receptors on targets), weight control
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What are the functions of the female reproductive system?
- Produces haploid gametes - Facilitate fertilisation with spermatozoan - Site for implantation of the embryo - Provide physical and nutritional needs to nurture baby (mammary glands)
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What are the ovaries?
Female gonads - mature ova Medulla - blood vessels and lymph Cortex - outer epithelia layer containing oocytes (in a follicle - folliculogenesis) Follicular cells secrete steroid hormones: - granulosa - 17b oestrogen - theca - progesterone Primary follicle - graafian follicle - corpus luteum
396
What are the fallopian tubes?
Transport egg to uterus - 10cm Has Isthmus -> ampulla -> infundibulum with fimbriae. Smooth muscle (circular & longitudinal) in walls - peristalsis Has highly folded mucosa - ciliated and secretory cells
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What are the walls of the uterus?
Perimetrium (outer) Myometrium Endometrium
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What is the endometrium?
Uterus inner layer Simple columnar with leukocytes and macrophages Lamina propria - lots of connective tissue Compound tubular glands Has spiral arteries
399
What is the cervix?
Connects uterus to vagina Has external and internal os Cervical glands secrete mucus - prevents microbes
400
What is the vagina?
Birth canal 8-10cm Thin wall of: - adventitia - muscularis - mucosa Has stratified squamous epithelium (with glycogen) which ferments to lactic acid to prevent bacteria Also has dendritic cells
401
What are the two female cycles?
Ovarian (follicular and luteal) and endometrial (menstrual) (menses, proliferative and secretory)
402
What drives the endometrial cycle?
The hypothalamic-pituitary-gonadal axis - hypothalamic neurones release gonadotropin-releasing hormones (GnRH) This travels to the anterior pituitary by the hypophyseal portal system GPCRs on pituitary (gonadotrophs) release gonadotropins: - FSH - LH
403
What do LH and FSH do?
Stim ovarian follicular cells to secrete steroid hormones: progesterone (theca cells) and 17b-oestrodoil (granulosa - these also release inhibin (decreases FSH) and activin (increases FSH)) This produces mature gametes LH - triggers ovulation FSH - grows and matures follicles
404
What regulates the ovarian cycle?
HPGA is controlled by +ve and -ve feedback Follicular phase: 17b-oestrodiol - -ve feedback Luteal phase: progesterone - -ve feedback Ovulation (midcycle): follicular cell proliferation, oestrodoil rapidly decreases - +ve feedback - more FSH/LH - triggers ovulation of oocyte
405
What happens at phases of ovarian cycle?
Follicular - FSH/LH - increases follicles so there is a surge of oestrogen as they are making more (proliferative phase) The oestrogen reaches a point where it causes positive feedback - LH and FSH - ovulation happens Luteal - corpus luteum secretes progesterone - this stimulates endometrial glands - they will secrete (secretory phase) At day 22 - corpus luteum will degenerate - endometrium is lost - as oestrogen and progesterone is falling
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What causes changes in endometrium?
17B-oestrodiol and progesterone cause the changes
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What happens to the mucus levels in the follicular and secretory phases?
Follicular: mucus copious, watery and elastic, forms channels to propel sperm Secretory: mucus is thick
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What is the proliferative phase?
In endometrial cycle 17B-oestrodiol increases loads Causes growth of: - endometrum - glands - stroma - spiral arteries elongate
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What is the secretory phase?
After ovulation - dominated by progesterone Proliferation slows - thickness decreases Glands have glycogen and mucus Spiral arteries elongate and coil Ends in menses
410
What are some hormonal contraceptives
- oestrogen and progesterone - decreases LH/FSH so no ovulation or folliculogenesis - progesterone only - monophasic (fixed dose) - multiphasic (varying dose)
411
How is Progestin a contraceptive?
Only progesterone Thick cervical mucus - no sperm penetration Less uterus and fallopian tube motility Less endometrial glycogen
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How does the morning after pill work?
High oestrogen and progesterone dose - interferes with implantation - inhibit ovulation - thickens mucus so sperm can't reach
413
How do contraceptives work?
Some feedback on hypothalamus - less GnRH - low FSH and LH - no ovulation or folliculogenesis
414
What is fertilisation?
Gametes are transported to the ampulla of the oviduct The oocyte is surrounded by granulosa cells Sperm(150-600 million): capacitation, SM contraction and cervical mucus helps the sperm The sperm penetrates via an acrosomal reaction This activates the oocyte - increases calcium - causes 2nd meiotic division and prevents another sperm in (polyploidy) The haploid pronuclei fuse = diploid zygote Happens early in fallopian tube
415
What happens after fertilisation?
Move along oviduct for three days - nourished by oviduct secretions - isthmus contractions slow it down to allow endometrium to prepare Will divide until 8 - then becomes morula then blastocyst - then implanted (6 days)
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What is the blastocyst?
Before implantation - fluid filled cavity. Lined by trophoectoderm layer - this makes the yolk sac, fetal placenta and amnion
417
What is implantation?
At 6-10 days after ovulation Blastocyst promotes stromal cells from endometrium to transform into decidual cells (predecidualisation) Endometrial reception to blastocyst - low oestrodiol:progesterone (secretory phase) There is several parts of the invasion
418
What are the trophoblastic cells?
In blastocyst: - inner cytotrophoblast: single mitotic layer which differentiates into syncytiotrophoblast - outer syncytiotrophoblast: produces hormones e.g. HCG
419
How does the blastocyst invade the endometrium?
1) Hatching: zona pellucida (outer layer) degenerates due to lytic factors - releasing inner cells 2) Apposition: the trophoblastic and endometrial epithelium meet 3) Adhesion: intracellular and extracellular integrins bind to receptors on the deciduous endometrium 4) Invasion: syncytiotrophoblast cells penetrates endometrium
420
What is the outer layer of the blastocyst called?
Zona pellucida
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How does the placenta develop?
Allows materials to pass from maternal system to foetus Have 120 spiral arteries from the mother - empty into intervillous places - washes over foetal projections and decreases the force from the mothers blood Syncytiotrophoblast lacunae - merge and fill with maternal blood Syncytiotrophoblast and cytotrophoblast form villi and microvilli
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How is foetal and maternal blood separated in the placenta?
- foetal capillary epithelium - mesenchyme - cytotrophoblasts - syncytiotrophoblasts
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What is transported between maternal and foetal blood?
From maternal: - glucose (fac diff) - amino acids (2nd active transport) - vitamins (active transport) - antibodies/hormones (endocytosis) From foetal: - waste urea and creatinine
424
What are the hormonal changes in trimester 1?
Trophoblast: HCG (rescues the corpus luteum) - up to week 9 Corpus luteum: progesterone and oestrogen to support endometrium
425
What happens in trimester 2/3?
Placenta: steroid hormones. This includes human placental lactogens (hCS) which: - coordinate fuel economy - develop mammary glands Progesterone from cholesterol Oestrogen from foetal-placental
426
What is stage 0 of parturition?
Stage 0 (quiescence): before birth, uterus is relaxed and insensitive to uterotonic hormones, progesterone suppresses myometrial contractions, braxton-hicks
427
What is stage 1 of parturition?
Stage 1 (activation): cortisol increases by H-P-adrenal axis - this increases oestrogen - contracts and stimulates prostaglandin release (promotes formation of gap junctions and softens and thins cervix) Contraction- associated proteins are expressed e.g. uterotonic recs of oxytocin Enzymes to hydrolyse collagen are expressed
428
What is stage 2 of parturition?
Stimulation of birth: PG increase: myometrial contraction, cervical dilation Increased myometrial connectivity and responsiveness positive feedback loops: ferguson reflex and uterine contraction increasing PG + oxytocin Labour: dilation --> expulsion --> placental
429
What is parturition stage 3?
Recovery from birth Haemostasis - vasoconstriction of spiral arteries Decrease in oestrogen - myometrium will regress The endometrial lining will reestablish after 3-5 months
430
What is lactation?
From secretory unit of breast = alveoli (contractile cells and adipose tissue) During pregnancy: oest and prog stim breast growth, oest will stimulate anterior pituitary to release prolactin but prog and oest prevent it acting on breast Postpartum: oest increases cell proliferation, prolactin initiates milk, oxytocin increases contraction and release of milk, prolactin and cortisol maintain milk
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What does prolactin do?
For milk production Inhibiting dopamine releases prolactin from anterior pituitary Oxytocin is released from posterior pituitary Downregulates GnRH to inhibit ovarian cycle
432
What is the spirometer graph?
Look on the lab on lt
433
Where do we place the lead II ecg electrodes?
+ve - left ankle -ve - right wrist earth - left wrist If the electrical vector moves towards +ve vector - positive defection
434
What are the AV valves?
Mitral - left Tricuspid - right